Deficiency in DNA repair can cause mutations, while dysfunctional transcription by AP-1 and p53 can cause uncontrolled cell proliferation. Both problems can lead to cancer. The major mammalian APendonuclease (Ape) protects cells by removing some of the most abundant mutagenic lesions from DNA: apurinic/apyrimidinic (AP) sites. Furthermore, Ape has other distinctive activities in vitro related to transcriptional regulation: as a redox factor to reductively activate transcription factors such as AP-1 and p53. My preliminary studies have shown that APE gene expression is cell growth-dependent in NIH3T3 cells. My hypothesis is that, transcription factor E2F interacts with the APE promoter and activates APE gene to enhance the roles of Ape protein in DNA repair and/or transcription factor regulation during the DNA replication S phase. To test this, I will use nuclear run-on, APE promoter-reporter, and RNA stability assays to determine whether the increases in APE mRNA are due to activation of the promoter or mRNA stabilization. Next, I will characterize the possible interaction between E2F and the APE promoter. Finally, to evaluate the effects of growth-dependent APE gene regulation on cell function, I will conduct in vitro enzyme activity assays and in vivo cell growth and cell survival assay after DNA damage.